Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population

Dendritic cells residing in the skin represent a large family of antigen-presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to various distinct classical dendritic cell subsets in the dermis. Through genetic fate mapping analysis and single-cell RNA-sequencing, we have...

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Published ineLife Vol. 10
Main Authors Sheng, Jianpeng, Chen, Qi, Wu, Xiaoting, Dong, Yu Wen, Mayer, Johannes, Zhang, Junlei, Wang, Lin, Bai, Xueli, Liang, Tingbo, Sung, Yang Ho, Goh, Wilson Wen Bin, Ronchese, Franca, Ruedl, Christiane
Format Journal Article
LanguageEnglish
Published England eLife Sciences Publications Ltd 26.03.2021
eLife Sciences Publications, Ltd
Subjects
Antigen presentation
Antigen-presenting cells
Bone marrow
CD8 antigen
Cell fate
Cell migration
Contact dermatitis
dendritic cell
Dendritic cells
Dermis
Effector cells
Epidermis
Fate maps
Flow cytometry
Gene mapping
Genetic analysis
Haptens
Hypersensitivity
Immunological tolerance
Immunology and Inflammation
Langerhans cell
Langerhans cells
lymph node
Lymph nodes
Lymphatic system
Lymphocytes T
Osteoprogenitor cells
Population
skin
Skin diseases
mouse
Langerhans cell
inflammation
lymph node
cell migration
skin
immunology
dendritic cell
dermis
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Abstract Dendritic cells residing in the skin represent a large family of antigen-presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to various distinct classical dendritic cell subsets in the dermis. Through genetic fate mapping analysis and single-cell RNA-sequencing, we have identified a novel separate population of LC-independent CD207 CD326 LC cells in the dermis that homed at a slow rate to the lymph nodes (LNs). These LC cells are long-lived and radio-resistant but, unlike LCs, they are gradually replenished by bone marrow-derived precursors under steady state. LC cells together with cDC1s are the main migratory CD207 CD326 cell fractions present in the LN and not, as currently assumed, LCs, which are barely detectable, if at all. Cutaneous tolerance to haptens depends on LC cells, whereas LCs suppress effector CD8 T-cell functions and inflammation locally in the skin during contact hypersensitivity. These findings bring new insights into the dynamism of cutaneous dendritic cells and their function opening novel avenues in the development of treatments to cure inflammatory skin disorders.
AbstractList Dendritic cells residing in the skin represent a large family of antigen-presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to various distinct classical dendritic cell subsets in the dermis. Through genetic fate mapping analysis and single-cell RNA-sequencing, we have identified a novel separate population of LC-independent CD207 + CD326 + LC like cells in the dermis that homed at a slow rate to the lymph nodes (LNs). These LC like cells are long-lived and radio-resistant but, unlike LCs, they are gradually replenished by bone marrow-derived precursors under steady state. LC like cells together with cDC1s are the main migratory CD207 + CD326 + cell fractions present in the LN and not, as currently assumed, LCs, which are barely detectable, if at all. Cutaneous tolerance to haptens depends on LC like cells, whereas LCs suppress effector CD8 + T-cell functions and inflammation locally in the skin during contact hypersensitivity. These findings bring new insights into the dynamism of cutaneous dendritic cells and their function opening novel avenues in the development of treatments to cure inflammatory skin disorders. Our immune cells are constantly on guard to defend and protect us against invading pathogens, such as bacteria and viruses. Specialized immune cells, known as antigen-presenting cells, or APCs, have a key role in this process. They engulf invaders, chew them up, and travel to the closest local lymph node to stimulate other immune cells with small fragments of these pathogens. This ramps up the immune response to control infection and disease. APCs are a large and diverse family of immune cells, which includes dendritic cells and macrophages. Some APCs work as mobile surveillance units, travelling around the body to find new threats. Others embed themselves in particular organs and tissues, such as the skin, to provide local, on-the-spot surveillance. Langerhans cells are one of the main types of APC in the skin and are found in the thin outer layer of the epidermis. While it is commonly believed that Langerhans cells can move from the epidermis to the skin-draining lymph nodes, some seemingly contradictory evidence exists to suggest that this may not be the case. Now, Sheng et al. have investigated this issue by tracking APCs, including Langerhans cells, in the skin of mice. A powerful genetic cell labelling technique allowed them to track the movement of immune cells inside a living mouse. Sheng et al. found that majority of 'real' Langerhans cells did not leave the skin. Yet, a second lookalike cell that shared many of the same features of a Langerhans cell was found in the dermal layer of skin, and this cell could travel to local lymph nodes. Both the original and lookalike cells had distinct and separate roles in the skin. This research, which has uncovered a new type of Langerhans-like immune cell in the skin, may be extremely useful for developing new targeted therapies to boost immune responses during infection; or to suppress inappropriate immune activation that can lead to autoimmune diseases, such as psoriasis.
Dendritic cells residing in the skin represent a large family of antigen-presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to various distinct classical dendritic cell subsets in the dermis. Through genetic fate mapping analysis and single-cell RNA-sequencing, we have identified a novel separate population of LC-independent CD207+CD326+ LClike cells in the dermis that homed at a slow rate to the lymph nodes (LNs). These LClike cells are long-lived and radio-resistant but, unlike LCs, they are gradually replenished by bone marrow-derived precursors under steady state. LClike cells together with cDC1s are the main migratory CD207+CD326+ cell fractions present in the LN and not, as currently assumed, LCs, which are barely detectable, if at all. Cutaneous tolerance to haptens depends on LClike cells, whereas LCs suppress effector CD8+ T-cell functions and inflammation locally in the skin during contact hypersensitivity. These findings bring new insights into the dynamism of cutaneous dendritic cells and their function opening novel avenues in the development of treatments to cure inflammatory skin disorders.
Dendritic cells residing in the skin represent a large family of antigen-presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to various distinct classical dendritic cell subsets in the dermis. Through genetic fate mapping analysis and single-cell RNA-sequencing, we have identified a novel separate population of LC-independent CD207 CD326 LC cells in the dermis that homed at a slow rate to the lymph nodes (LNs). These LC cells are long-lived and radio-resistant but, unlike LCs, they are gradually replenished by bone marrow-derived precursors under steady state. LC cells together with cDC1s are the main migratory CD207 CD326 cell fractions present in the LN and not, as currently assumed, LCs, which are barely detectable, if at all. Cutaneous tolerance to haptens depends on LC cells, whereas LCs suppress effector CD8 T-cell functions and inflammation locally in the skin during contact hypersensitivity. These findings bring new insights into the dynamism of cutaneous dendritic cells and their function opening novel avenues in the development of treatments to cure inflammatory skin disorders.
Author Liang, Tingbo
Sung, Yang Ho
Chen, Qi
Mayer, Johannes
Zhang, Junlei
Bai, Xueli
Sheng, Jianpeng
Ronchese, Franca
Wang, Lin
Goh, Wilson Wen Bin
Ruedl, Christiane
Wu, Xiaoting
Dong, Yu Wen
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33769279$$D View this record in MEDLINE/PubMed
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Keywords mouse
Langerhans cell
inflammation
lymph node
cell migration
skin
immunology
dendritic cell
dermis
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Snippet Dendritic cells residing in the skin represent a large family of antigen-presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to...
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SubjectTerms Antigen presentation
Antigen-presenting cells
Bone marrow
CD8 antigen
Cell fate
Cell migration
Contact dermatitis
dendritic cell
Dendritic cells
Dermis
Effector cells
Epidermis
Fate maps
Flow cytometry
Gene mapping
Genetic analysis
Haptens
Hypersensitivity
Immunological tolerance
Immunology and Inflammation
Langerhans cell
Langerhans cells
lymph node
Lymph nodes
Lymphatic system
Lymphocytes T
Osteoprogenitor cells
Population
skin
Skin diseases
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Title Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population
URI https://www.ncbi.nlm.nih.gov/pubmed/33769279
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Volume 10
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